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Page 1 Saif Aljabab 2011 Gillian Lieberman, MD March 2011 Nanotechnology in Diagnostic Imaging Saif Aljabab , King Saud University VI Gillian Lieberman, MD March 18, 2011
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Saif
Aljabab
2011
Gillian Lieberman, MD March 2011
Nanotechnology in
Diagnostic Imaging
Saif
Aljabab
, King Saud
University
VIGillian Lieberman, MD
March 18, 2011
Page 2
Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?• Why Nano‐material properties change?• Nanotechnology Applications.• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 1
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Agenda• Our Patients Presentation.
• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?• Why Nano‐material properties change?• Nanotechnology Applications.• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
49 Year old Female, known to have osteoporosis presented to the clinic with intermittent constipation, nausea & vomiting.
•
she passed 2 kidney stones last year, she had a bone lesion 7 months ago in the right tibia that was diagnosed as osteitis
fibrosa
cystica.
•
No significant past medical or surgical illnesses, non smoker on vitamin D supplements & bisphosphonates.
Our Patient:History
Saif
Aljabab
2011
Gillian Lieberman, MD
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• Patient is lethargic but not in pain or distress.• Vitals are stable.• Chest clear, bilateral air entry , no wheezing.• CVS Normal S1+S2+0• Abdomen soft lax , non tender & bowl sounds present.
• Some swelling at the mid portion of the right tibia• No other significant findings
Our Patient:Physical Examination
Saif
Aljabab
2011
Gillian Lieberman, MD
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• CBC : Normal
• U/E: Serum Ca+ 14.7 mg/dL (High)
• Urinary Ca+ >400mg (High)
• PTH: 107 (High)
Our Patient:Labs
Saif
Aljabab
2011
Gillian Lieberman, MD
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• Our Patient was diagnosed with primary hyperparathyroidism.
• We ordered a parathyroid Ultrasound & Nuclear scan to identify the culprit gland.
Our Patient:Investigation Plan
Saif
Aljabab
2011
Gillian Lieberman, MD
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PACS, BIDMC
Our Patient:Right Inferior Parathyroid Adenoma on
Ultrasound
Saif
Aljabab
2011
Gillian Lieberman, MD
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PACS, BIDMC
Rt
Jugular
Vein
Strip
Muscles
Inferior Rt
Parathyroid
Parts of
arterial
vessels
Our Patient:Right Inferior Parathyroid Adenoma on
Ultrasound
Saif
Aljabab
2011
Gillian Lieberman, MD
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Our Patient:Color Doppler showing avascular adenoma at
same location
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 9
PACS, BIDMC
Page 11
Inferior Rt
Parathyroid
Our Patient:Color Doppler showing avascular adenoma at
same location
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 10
PACS, BIDMC
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Our Patient:Rt Inferior Adenoma on Sestamibi Scan
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 11PACS, BIDMC
Courtesy of: Kevin Donohoe, MD
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Inferior Rt
Parathyroid
Parotid
Gland
Submandibla
r Glands
Thyroid
Gland
Heart
NoseMouth
Our Patient:Rt Inferior Adenoma on Sestamibi Scan
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 12PACS, BIDMC
Courtesy of: Kevin Donohoe, MD
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Our Patient:Rt Inferior Adenoma on Sestamibi Scan
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 13
PACS, BIDMC
Courtesy of: Kevin Donohoe, MD
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Inferior Rt
Parathyroid
Our Patient:Rt Inferior Adenoma on Sestamibi Scan
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 14
PACS, BIDMC
Courtesy of: Kevin Donohoe, MD
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•Differential Diagnosis of a mass in the parathyroid that may give symptoms of primary hyperparathyroidism:
•Parathyroid Adenoma.•Parathyroid Hyperplasia.•Parathyroid Carcinoma.
Our Patient:Differential Diagnosis
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
Medical Management: Estrogen if patient is post‐menopause to prevent osteoporosis / Bisphosphonates
to control hypercalcaemia.
•
Surgical Management: Surgical Removal of the culprit gland while monitoring Parathyroid hormone levels.
• Our patient went for surgical parathyroidectomy.
Our Patient:Management Plans
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
Surgery: The adenoma was sitting immediately below the lower lobe as predicted. The upper left parathyroid was enlarged as well, parathyroid hormone level post‐op was 23
after both were removed.
• Pathology: Right lower parathyroid (A); Cellular parathyroid tissue , consistent with parathyroid adenoma.Upper left parathyroid (B); Cellular parathyroid tissue consistent with parathyroid adenoma
Our Patient:Surgical & Pathological Results
Saif
Aljabab
2011
Gillian Lieberman, MD
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Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.
• What is Nanotechnology/Nanomedicine?• Why Nano‐material properties change?• Nanotechnology Applications.• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 18
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•
In our patient we missed the left upper adenoma, in most cases the Sestamibi
scan will show the
presence & location of an adenoma, confirmed by ultrasound results.
•
However, current imaging modalities miss the location of an adenoma in few cases, difficulty in localization escalates as we try to identify a carcinoma & its possible metastasis.
Challenges we faced with our patient
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
Mixed results can happen, where ultrasounds identify a different location of an adenoma than a Sestamibi
scan, in some cases the
surgeon identifies a third location.
•
Currently PET, SPECT, MRI, CT & U/S are the most modalities of imaging used to diagnose, localize, stage & follow up with cancer patients.
Saif
Aljabab
2011
Gillian Lieberman, MD
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The Need to Improve
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•
These modalities are quite useful clinically but are not perfect, and its accuracy falls down even more when trying to detect micro metastasis.
•
This raises the issue that we need to find new more improved ways to detect tumors accurately.
Saif
Aljabab
2011
Gillian Lieberman, MD
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The Need to Improve
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Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?
• Why Nano‐material properties change?• Nanotechnology Applications.• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
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NanoTechnology has a potential role in detecting tumors more accurately
www.theage.com.au
Saif
Aljabab
2011
Gillian Lieberman, MD
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Ant Holding a Microchip
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•
What is 100,000 times thinner than a strand of hair & 20 times tougher than steel?
A Carbon Nano‐Tube(1×
10−9 m)
What is a Nano?
http://www.nsf.gov/od/lpa/news/03/pr03147.htm
Saif
Aljabab
2011
Gillian Lieberman, MD
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• Its not biology, physics or chemistry its all sciences that deal with such a small scale.
•
Best Definition: “Encompasses the common unifying concepts & physical laws that prevail in the Nano
scale “
www.nanoscience‐europe.org
What is Nano Technology?Saif
Aljabab
2011
Gillian Lieberman, MD
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•
Nanomedicine
may be defined as the monitoring, repair, construction and control of human biological systems at the molecular level, using engineered Nanodevices
and Nanostructures.
What is Nano‐Medicine?Saif
Aljabab
2011
Gillian Lieberman, MD
Page 26Robert A. Freitas
Jr
“Nanomedicine” 1998‐2006 http://www.foresight.org/Nanomedicine/
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• Humans have unwittingly employed nanotechnology for thousands of years.
Nanotechnology in History
Http://www.wired.com –http://steelguru.com/article/details/NiI%3D/Damascus_Sword.html
Saif
Aljabab
2011
Gillian Lieberman, MD
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Damascus Steel, a type of steel used in sword making from 300 BC –1700 AD was discovered to contain nanowires
& nano
carbontubes.
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• When it comes to Nature, they are the king of nanotechnology.
Nanotechnology in Nature
http://micro.magnet.fsu.edu/cells/ciliaandflagella/ciliaandflagella.html
Saif
Aljabab
2011
Gillian Lieberman, MD
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A flagella structure is a complexity of Nanorotors, motors, tubes & arms that work perfectly together, many of which we still try to decipher how they work.
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Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?• Why Nanomaterial properties change?
• Nanotechnology Applications.• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
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• When everyday material is converted to a Nanoscale they start to act in unpredictable ways.
•
Many of the physical properties of substances we know change at this scale, as if projecting the tablet of elements into several dimensions.
• Understanding how they start to work and what physical properties change can be tricky.
Physical Properties changeSaif
Aljabab
2011
Gillian Lieberman, MD
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•
When items are turned this small, the movement space of its electrons becomes much more limited than it prefers, this increases its kinetic energy, gaining it more speed.
Theory Behind Properties Changes:1‐ Quantum Confinement
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
Things this small have much more outside than inside, most of the material may be surface and very little can be volume.
Theory Behind Properties Changes:2‐ Surface to Volume Ratio
Saif
Aljabab
2011
Gillian Lieberman, MD
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Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?• Why Nano‐material properties change?• Nanotechnology Applications.
• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
Over 600 products in the market currently use nanotechnology, from gulf clubs to Nanotexclothing, cosmetics, paints to Solar energy cells, water filters.
Nanotechnology Applications
http://oecotextiles.wordpress.com/2010/02/10/what‐about‐soil‐resistant‐finishes‐like‐scotchgard‐goretex‐nanotex‐and‐greenshield‐are‐they‐safe/
Saif
Aljabab
2011
Gillian Lieberman, MD
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Nanotex
clothing are resistant to liquid stains, you can spill what you want on it.
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Applications in Medicine
huffingtonpost.com
• Radiation Therapy, drug delivery systems, regenerative medicine, biosensors for detecting salmonella in food products, tissue engineering, dendrimers
in gene therapy.
• Opens the era of personalized medicine.
Saif
Aljabab
2011
Gillian Lieberman, MD
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Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?• Why Nano‐material properties change?• Nanotechnology Applications.• Nano
Applications in Diagnostic Imaging.
• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
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• Currently using Nano‐particles is the mainstay of research in enhancing diagnostic imaging.
•
There are 4 major advantages that these Nano‐particles give to improve imaging in comparison to other techniques like Molecular imaging.
Nano Application in Diagnostic ImagingSaif
Aljabab
2011
Gillian Lieberman, MD
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1‐
Larger surface allows for a multi functional ability
in interacting with more molecular agents/particles.
2‐ A
Stronger Amplifier
of signals that can be detected outside the body which may help detect micro metastasis.
3‐Multi modality competence
, in that it can enhance signaling of several imaging modalities.
4‐ Both diagnostic & therapeutic (theranostic) potential.
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 38Sanjiv
Sam Gambhir, M.D., Ph.D; Nanotechnology in Cancer Imaging, Dec 17 2010
Molecular Imaging Center at Stanford School of Medicine http://nano.cancer.gov/learn/impact/podcasts.asp#annabarker.
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•
Gold(Au) Nano‐particles are a versatile material whose natural resistance to surface oxidation makes it ideal for a wide‐range of research applications,.
•
These particles are being used now in research to detect colorectal cancer, specially flat lesions that are difficult to see on colonoscopy, the gold nanoparticlescan be detected using a Raman spectroscopy..
Examples of Nano Diagnostic ImagingSaif
Aljabab
2011
Gillian Lieberman, MD
Page 39Sanjiv
Sam Gambhir, M.D., Ph.D; Nanotechnology in Cancer Imaging, Dec 17 2010
Molecular Imaging Center at Stanford School of Medicine http://nano.cancer.gov/learn/impact/podcasts.asp#annabarker.
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Examples of Nano Diagnostic Imaging
http://www.fleetattorney.net/tag/colon‐cancer/
Saif
Aljabab
2011
Gillian Lieberman, MD
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• Photo‐Acoustic Imaging Nano‐particles, these particles are used in research to develop a new modality of detecting tumors.
• Light enters the body heating the particles enough to produce asound ‐but not enough to harm tissue‐
that can be detected by an
external source.• Example of such particles that can be used are Carbon nanotubes& Gold nanoparticles modified to emit sounds.
Examples of Nano Diagnostic ImagingSaif
Aljabab
2011
Gillian Lieberman, MD
Page 41Sanjiv
Sam Gambhir, M.D., Ph.D; Nanotechnology in Cancer Imaging, Dec 17 2010
Molecular Imaging Center at Stanford School of Medicine http://nano.cancer.gov/learn/impact/podcasts.asp#annabarker.
Sound
waves
Page 43
•Iron nanoparticles
which are iron oxide nanoparticlescoated with dextran
are another example of nanoparticles
used in diagnostic imaging.
•These particles are mainly used to target lymph nodes for cancer spread detecting it with MRI.
•The particles are taken up by normal cells in the lymph node but not by cancer cells.
Saif
Aljabab
2011
Gillian Lieberman, MD
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Examples of Nano Diagnostic Imaging
Ralph Weissleder
MD, Mukesh
Harisinghani
MD, Donald Kaufman MD, Stealth Imaging with iron nanoparticles, Mass General Hospital 2008, http://nanomedicine‐explorer.net/stories/stealthiron/overview‐2.html.
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•
Patients would first take an MRI, afterwards be injected with Iron nanoparticles
then
take another MRI image after 24 hours.
•
Lymph nodes that take the nanoparticleswill change color to black, cancer cells will stay bright.
Saif
Aljabab
2011
Gillian Lieberman, MD
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Examples of Nano Diagnostic Imaging
Ralph Weissleder
MD, Mukesh
Harisinghani
MD, Donald Kaufman MD, Stealth Imaging with iron nanoparticles, Mass General Hospital 2008, http://nanomedicine‐explorer.net/stories/stealthiron/overview‐2.html.
Page 45http://www.prostatecancer.org/pcricms/node/172
Saif
Aljabab
2011
Gillian Lieberman, MD
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MRI: Lymph node before & after
injecting with Iron nanoparticles
http://www.prostate‐cancer.org/pcricms/node/172
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•Gold nanoshelled
microcapsules are a combination of electrostatic gold nanoparticle
depositions onto
microcapsules and a surface seeding method which results in the formation of gold nanoshells.
•This nano/microcomposite
is able to operate as a theranostic
agent for both contrast‐enhanced ultrasonic
imaging (diagnostic) and photo hyperthermia (therapeutic), and thus holds a great potential for photothermal
therapy in cancer treatment.
Examples of Nano Diagnostic Imaging
KeH, Wang J, Dai Z, Jin Y, Qu E, Xing Z, Guo C, Yue X, Liu J. Goldnanoshelled
microcapsules: a theranostic
agent for
ultrasound contrast imaging and photothermal
therapy. Angew Chem Int Ed Engl. 2011 Mar 21;50(13):3017‐21
Saif
Aljabab
2011
Gillian Lieberman, MD
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Image of a Gold Nanoshell
Ke H, Wang J, Dai Z, Jin Y, Qu E, Xing Z, Guo C, Yue X, Liu J. Goldnanoshelled
microcapsules: a theranostic
agent for
ultrasound contrast imaging and photothermal
therapy. Angew Chem Int Ed Engl. 2011 Mar 21;50(13):3017‐21
Saif
Aljabab
2011
Gillian Lieberman, MD
Page 46
http://onlinelibrary.wiley.com/doi/10.1002/anie.201008286/abstract
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Agenda• Our Patients Presentation.• Current challenges in Imaging Modalities.• What is Nanotechnology/Nanomedicine?• Why Nano‐material properties change?• Nanotechnology Applications.• Nano Applications in Diagnostic Imaging.• Dangers behind using Nano.
Saif
Aljabab
2011
Gillian Lieberman, MD
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•
With the development of nanomaterial's, environmental & health concerns are mounting about exposure & its safety regulations.
•
For example respirator filter masks may not protect against Nano
particles being inhaled!!
They can pass through normal human protective barriers and reach the deepest structures within our tissue reacting with them.
Dangers Behind Using NanoSaif
Aljabab
2011
Gillian Lieberman, MD
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•
A research model on rats which made them inhale carbon nanotubes
showed that their
lungs did react to the nanoparticles
and inflammation was noted, most of the inflammation did clear out with time.
•
Currently there is lack in regulation of nanoproduction on companies due to the very little data available on its toxicity.
•
Dangers Behind Using NanoSaif
Aljabab
2011
Gillian Lieberman, MD
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AcknowledgmentsI would like to thank the following for their
help and support in preparing this presentation:
Kevin Donohoe, MDGerald Kolodny, MDGillian Lieberman, MDRafael Rojas, MDEmily Hanson
Saif
Aljabab
2011
Gillian Lieberman, MD
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• P. Fleckenstein , J. Tranum Jensen; Anatomy in Diagnostic Imaging
, 2nd Ed.; Neck: 263‐271.• John C. Harbert, William C. Eckelman, Ronald D. Nermann; Nuclear Medicine Diagnosis & Therapy 21:
429‐438.• Douglas Katz MD, Kevin Math MD, Stuart Groskin MD; Radiology Secrets 83: 531‐535, 1998.• Nanotechnology in Medicine Lecture by Dr. T.V. RAD, http://www.slideworld.org/slideshow.aspx.• Nanotechnology Introductory series lectures, http://www.kqed.org/quest/television/view.• Sanjiv Sam Gambhir, M.D., Ph.D; Nanotechnology in Cancer Imaging, Dec 17 2010
http://nano.cancer.gov/learn/impact/podcasts.asp#annabarker.
• Ralph Weissleder MD, Mukesh Harisinghani MD, Donald Kaufman MD, Stealth Imaging with iron
nanoparticles
2008, http://nanomedicine‐explorer.net/stories/stealthiron/overview‐2.html.• Article on Nanotechnology; http://en.wikipedia.org/wiki/Nanotechnology.• Nanotechnology in Medicine Application: Diagnostic and Imaging Techniques;
http://www.understandingnano.com/medicine.html.• Ke H, Wang J, Dai Z, Jin Y, Qu E, Xing Z, Guo C, Yue X, Liu J. Goldnanoshelled
microcapsules: a theranostic
agent for ultrasound contrast imaging and photothermal
therapy. 2011 Mar 21;50(13):3017‐21. • http://www.uptodate.com/• Robert A. Freitas
Jr
“Nanomedicine” 1998‐2006 http://www.foresight.org/Nanomedicine• Beth Isreal Deconess Hospital Careweb Portal .•
Images from:
http://www.fleetattorney.net/tag/colon‐cancer/ || http://www.fleetattorney.net/tag/colon‐cancer/||http://www.prostatecancer.org/pcricms/node/172 ||www.theage.com.au||Http://www.wired.com || http://www.nsf.gov/od/lpa/news/03/pr03147.htm || http://steelguru.com/article/details/NiI%3D/Damascus_Sword.html || http://micro.magnet.fsu.edu/cells/ciliaandflagella/ciliaandflagella.html
|| http://oecotextiles.wordpress.com/2010/02/10/what‐about‐soil‐resistant‐finishes‐like‐scotchgard‐goretex‐nanotex‐and‐greenshield‐are‐they‐safe/ || huffingtonpost.com
• http://onlinelibrary.wiley.com/doi/10.1002/anie.201008286/abstract
References
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« It’s a Small World After All »Thank You
Saif
Aljabab
2011
Gillian Lieberman, MD March 2011
